This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are investigating applications of head-fixed recurrent brain-computer interfaces [R-BCI] that operate continuously during free behavior and generate activity-dependent stimulation of the brain, spinal cord or muscles. These so-called "Neurochips" consist of printed circuit boards populated with off-the-shelf components and are connected to electrodes that record the activity of cortical cells and/or muscles. The neural activity is processed by programmable computer chips and can be converted in real-time to activity-contingent electrical stimuli delivered to nervous system sites or muscles. The autonomous operation of such artificial recurrent connections for days of unrestricted activity could allow subjects to incorporate them into normal behavior. A promising application is to bridge impaired biological connections, as we demonstrated for cortically controlled functional electrical stimulation of transiently paralyzed forearm muscles (shown so far mainly via laboratory instrumentation). A second application is to produce synaptic plasticity through spike-triggered stimulation, which can strengthen weak physiological connections. The R-BCI paradigm has numerous potential applications, depending on the input signals, the computed transform and the output targets. We are currently exploring several new applications. We have shown that cortical stimulation triggered from forearm EMG can rapidly produce changes in cortical circuits. Cortically controlled intraspinal stimulation has produced changes in the response properties of cortical cells and has strengthened corticospinal pathways. We are also testing the induction of conditioned changes in intracortical connections with minimally invasive cortical surface electrodes. We have also shown that the R-BCI can be used for operant conditioning of activity during free behavior by delivering reinforcing intracranial stimulation contingent on EMG or neural activity. These studies indicate that the R-BCI has clinical potential to aid patients paralyzed by ALS or spinal injury to regain some motor control directly from cortical cells and may also be used to strengthen weak connections impaired by stroke.